TY - JOUR AB - Nefopam, an analgesic drug, effectively elicits antinociception in the majority of noxious and thermal models in rodents. Acetaminophen is among the most commonly used analgesic and antipyretic drugs worldwide, either on prescription or over the counter. The present study aimed to investigate the analgesic activity of nefopam combined with acetaminophen, which was expected to maximize the potency of analgesia and decrease the dose of nefopam required. Three series of experiments, namely acetic acid‑induced writhing tests in mice, hot plate tests in mice and tail flick tests in rats, were used to evaluate the analgesic effect. Initially, an optimum proportion of the two drugs, 3.5 mg/kg nefopam (N) + 60 mg/kg acetaminophen (A), was determined by orthogonal array design based on writhing response number. Subsequently, combinations of N and A (1.75 N + 30 A, 3.5 N + 60 A and 7.0 N + 120 A mg/kg) were determined to elicit antinociception in the writhing test (P<0.01 vs. normal saline control) in a dose-dependent manner. In the hot plate test, hot plate latencies up to 60 min after drug treatment were observed. The combination of 7.0 N + 120 A mg/kg exerted a greater cumulative antinociceptive effect throughout the observation period, with an area under the curve value of 1,156.95±199.30 area units (AU), compared with that achieved by 7.0 N mg/kg alone (632.12±62.38 AU). Furthermore, both monotherapy and compound therapy exhibited antinociception dose‑dependently in the tail-flick test. However, a combination of 5.0 N + 84 A mg/kg exerted greater analgesic effect compared with 5.0 N mg/kg alone. The data obtained demonstrate that acetaminophen may enhance the antinociceptive activity of nefopam. Thus, coadministration of nefopam with acetaminophen warrants clinical evaluation. AD - Department of Pharmacology, School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, P.R. China AU - Li,Qian AU - Zhuang,Quankun AU - Gu,Yaru AU - Dai,Cailing AU - Gao,Xiaoxiao AU - Wang,Xiaomin AU - Wen,Huimin AU - Li,Xin AU - Zhang,Yuyang DA - 2018/02/01 DO - 10.3892/br.2017.1032 EP - 183 IS - 2 JO - Biomed Rep KW - mice rats analgesic effects acetaminophen nefopam combination PY - 2018 SN - 2049-9434 2049-9442 SP - 176 ST - Enhanced analgesic effects of nefopam in combination with acetaminophen in rodents T2 - Biomedical Reports TI - Enhanced analgesic effects of nefopam in combination with acetaminophen in rodents UR - https://doi.org/10.3892/br.2017.1032 VL - 8 ER -